The RPE cell plays a basic role in maintaining the structural and physiological integrity of the neural retina. Alterations in its structural and functional actions can result in loss of photoreceptors and vision. We have studied the RPE cell extensively as an important immunoregulatory cell within the posterior pole of the eye. Our research activities on RPE cells can be subdivided into three categories: normal cell function studies, cytokine interactions and infectious processes. Cytokines, such as interferon (IFN)-gamma and IL-2, are a group of specialized hormone-like proteins which exert profound influences on cellular development and on a variety of cellular functions. This project has concentrated on studying the ways in which cytokines interact with cells of the immune system and with cells in the ocular microenvironment. These studies indicate that cytokine-mediated activation of RPE cells may be a basic component of ocular immunity and an important aspect of RPE cell transplantation. During the past year, we have studied the Toll-Like receptors (TLR). TLRs are a family of innate immune recognition receptors that recognize molecular patterns associated with microbial pathogens. Reactivity with the TLR on a cell induces antimicrobial immune responses. We investigated and compared the gene expression and cytoplasmic protein levels of TLRs in HRPE and in human monocyte cells (U937). Basal levels of TLR gene expression in HRPE was detected for TLR 1,2,3,4,5,and 9. TLR gene expression and protein levels were enhanced in HRPE cells treated with IFN-gamma and LPS. The differential patterns of expression of TLRs in HRPE and U937 cells suggest that retinal cells and monocytes respond differentially to microbial products. IFN-gamma, elevated during inflammatory and infectious diseases, can up regulate selective TLRs in HRPE and may thereby participate in immunopathogenic processes.